Simonini Gabriele, Masi Laura, Giani Teresa, Piscitelli Elisabetta, Cimaz Rolando, Vierucci Silvia, Brandi Maria Luisa, Falcini Fernanda
Department of Paediatrics, Rheumatology Unit, University of Florence, Florence, Italy.
J Rheumatol. 2005 Nov;32(11):2233-8.
Emerging evidence from in vitro studies and mouse genetics attributes to osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, an important role in vascular biology. We evaluated serum levels of OPG in a group of children with Kawasaki disease (KD), before immunoglobulin (IVIG) infusion and at 3-month followup.
Fifty patients (38 boys, 20 girls, median age 3.6 yrs, range 4 mo-7.4 yrs) fulfilling criteria for the diagnosis of KD, 30 febrile controls with infectious diseases, 18 patients with juvenile systemic lupus erythematosus (JSLE), and 40 healthy controls were enrolled. All KD patients received IVIG treatment within the first 10 days of illness, and aspirin. Coronary artery abnormalities (CAA) were reported in 6 out of 58 patients; all were male and younger than 5 years. Serum OPG was measured by ELISA in patients with KD before IVIG and at 3-month followup (median time 3.2 mo, range 3-3.5).
At baseline and at the 3-month followup, KD patients had significantly higher OPG serum levels than febrile controls (p < 0.001 and p < 0.004, respectively), JSLE patients (p < 0.0001), and healthy controls (p < 0.0001). At baseline, KD patients who developed CAA had higher OPG serum levels than those without CAA (p = 0.0001); this difference was not present at 3-month followup. The optimal OPG cutoff value of 123.2 pg/ml was a significant predictor for CAA, with a sensitivity of 100% (6/6), a specificity of 96% (50/52), and a positive predictive value of 75% (6/8).
High OPG levels might be the result of compensatory production during acute and subacute phases of KD. OPG assay might be an additional clinically useful marker to monitor and differentiate patients who develop, from those who do not develop, such coronary artery abnormalities.
体外研究和小鼠遗传学的新证据表明,肿瘤坏死因子受体家族成员骨保护素(OPG)在血管生物学中起重要作用。我们评估了一组川崎病(KD)患儿在静脉注射免疫球蛋白(IVIG)前及3个月随访时的血清OPG水平。
纳入50例符合KD诊断标准的患者(38例男孩,20例女孩,中位年龄3.6岁,范围4个月至7.4岁)、30例患有感染性疾病的发热对照、18例青少年系统性红斑狼疮(JSLE)患者和40例健康对照。所有KD患者在发病的前10天内接受IVIG治疗及阿司匹林治疗。58例患者中有6例报告有冠状动脉异常(CAA);均为男性且年龄小于5岁。通过酶联免疫吸附测定(ELISA)法检测KD患者在IVIG治疗前及3个月随访时(中位时间3.2个月,范围3至3.5个月)的血清OPG水平。
在基线及3个月随访时,KD患者的血清OPG水平显著高于发热对照(分别为p < 0.001和p < 0.004)、JSLE患者(p < 0.0001)及健康对照(p < 0.0001)。在基线时,发生CAA的KD患者血清OPG水平高于未发生CAA的患者(p = 0.0001);在3个月随访时这种差异不存在。OPG的最佳临界值为123.2 pg/ml,是CAA的显著预测指标,敏感性为100%(6/6),特异性为96%(50/52),阳性预测值为75%(6/8)。
高OPG水平可能是KD急性和亚急性期代偿性产生的结果。OPG检测可能是监测和区分发生与未发生此类冠状动脉异常患者的另一个临床有用标志物。